Serotonin-selective reuptake inhibitors （SSRIs）， as widely used antidepressants in clinical practice， exhibit significant individual differences in antidepressant efficacy. Gut microbiota plays an important role in the development and progression of depression， and the use of SSRIs exerts a significant impact on the gut microbiota of patients with depression. Based on this， this article reviews the research progress on the interactions between the antidepressant effects of SSRIs and gut microbiota. It has been found that SSRIs can influence the diversity， abundance， and function of the gut microbiota directly or indirectly. Conversely， the composition of the gut microbiota and differences in its functional metabolic pathways， and other factors， can in turn affect the antidepressant effects of SSRIs. Therefore， in clinical practice， gut microbiota diversity can be utilized as a predictive indicator for the antidepressant effects of SSRIs. Probiotics can be employed as an adjunct therapy alongside SSRIs， and dietary adjustments， as well as fecal microbiota transplantation， can be used to enhance the therapeutic efficacy of SSRIs. In the future， large-scale， multicenter clinical studies should be conducted， enrolling a broadly representative cohort of patients with depression， to uncover the true association between the antidepressant effects of SSRIs and gut microbiota， thereby opening up more effective avenues for the comprehensive treatment of depression.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

OBJECTIVE To design the implementation path around the key links of the management in the clinical comprehensive evaluation of drug in China， and to provide suggestions for optimizing and perfecting the management in the clinical comprehensive evaluation of drug. METHODS Based on the relevant experience of drug evaluation management in typical countries regions at home and abroad， the discussion was performed and the management mechanism was designed from seven aspects， such as funding source， selection of topics， staff management， information management， data management， evaluation process and quality assessment. RESULTS & CONCLUSIONS In terms of funding sources， the financial department can provide funding guarantees or other alternative forms such as performance evaluations to encourage all parties to undertake the clinical comprehensive evaluation of drug projects. In terms of the selection of topics， a “top-down” or “bottom-up” selection mode can be determined according to the project’s nature and actual situation， and a selection process of “forming alternatives-setting up theme selection list-demonstrating and publishing theme selection list” can be formed. In terms of staff management， the specialty of team members should be specified， and the expert team should be established to provide clinical comprehensive evaluation of drug. In terms of information management， the national/provincial basic informational platform should be established， and the registration system should be established. In terms of data management， a regional health data-sharing platform should be formed and the “application-checking-utilization” mechanism should be conducted. In terms of the evaluation process， the evaluation procedures that concern on project implementation plan demonstration system and project closing review system should be constructed. In terms of quality assessment， quality assessment and reward and punishment mechanism for project completion，that consider the quality of management first while focusing on the technical quality， can be established. The management mechanism based on the standardized implementation of the seven key links will standardize the development of clinical comprehensive evaluation of drugs in China to some extent， and help improve the quality of clinical comprehensive evaluation projects for drugs.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

OBJECTIVE To establish the quality control method of Flueggea suffruticosa. METHODS The microscopical identification and thin layer chromatography （TLC） of F. suffruticosa were carried out， and the mass fractions of moisture， total ash， acid-insoluble ash and alcohol-soluble extracts in F. suffruticosa were measured based on the 2020 version of Chinese Pharmacopoeia （part Ⅳ）. The content of securinine in medicinal materials was determined by high performance liquid chromatography. RESULTS The powder of F. suffruticosa was gray-green， with obvious microscopic characteristics such as pores， pollen grains， calcium oxalate cluster crystals， ducts. The results of TLC identification showed that in the chromatograms of 16 batches of medicinal samples， the same color spots were found on the corresponding positions of the chromatograms of securinine， rutin， quercetin and F. suffruticosa control. The average mass fractions of moisture， total ash， acid-insoluble ash and alcohol- soluble extracts in 16 batches of medicinal materials were 9.26%， 6.96%， 1.17% and 28.89%， respectively. The injection volume of securinine in the range of 0.052 4-0.524 0 µg had a good linear relationship with the peak area （R2＝0.999 8）. RSDs of precision， repeatability and stability （24 h） test were all less than 3% （n＝6 or 7）. The average recovery of sample was 97.47%， RSD was 1.63% （n＝6）. The content of securinine in 16 batches of medicinal materials was 1.003-6.872 mg/g. CONCLUSIONS The quality control method of F. suffruticosa is established， and the mass fractions of moisture， total ash and acid-insoluble ash should not exceed 12.0%， 9.0% and 2.0%， respectively； the alcohol-soluble extract should not be less than 20%， and the content of securinine should not be less than 1.00 mg/g.

Objective:To evaluate the benefits and risks of advanced age patients with acute anterior circulation large vessel occlusive stroke (ALVOS) accepted mechanical thrombectomy (MT), and explore the related influencing factors for prognoses in these patients.Methods:Six hundred and eighty patients with acute anterior circulation ALVOS accepted MT in 3 comprehensive stroke centers from January 2014 to December 2020 were sequentially collected. (1) Patients were divided into advanced age group (≥80 years old) and non-advanced age group (<80 years old) according to age, and the differences between the two groups were compared in successful postoperative vascular recanalization rate, incidence of perioperative complications, and good prognosis rate (modified Rankin scale [mRS] scores≤2) and mortality 90 d after onset. (2) Patients were divided into good prognosis group (mRS scores≤2) and poor prognosis group (mRS scores>2) according to the prognoses 90 d after onset; univariate analysis and multivariate Logistic regression analysis were used to investigate the independent factors for prognoses of the patients after MT. (3) According to the prognoses 90 d after onset, the advanced age patients were divided into good prognosis subgroup (mRS scores≤2) and poor prognosis subgroup (mRS scores>2). Univariate analysis and multivariate Logistic regression analysis were used to investigate the independent factors for prognoses of the elderly patients after MT.Results:(1) In these 680 patients, 92 patients (13.5%) were into the advanced age group and 588 patients (86.5%) were in the non-advanced age group; patients in the advanced age group had significantly lower successful recanalization rate (67.4% vs. 77.9%), significantly lower good prognosis rate 90 d after onset (20.7% vs. 50.2%), and statically higher mortality 90 d after onset (40.2% vs. 21.1%) as compared with the non-advanced age group ( P<0.05); however, there was no significant difference between the two groups in the incidences of symptomatic intracranial hemorrhage (sICH, 15.6% vs. 10.6%) and malignant cerebral edema (MCE, 12.2% vs. 17.6%, P>0.05). The baseline data of the advanced age and non-advanced age patients were further matched with propensity score matching analysis (1:1) and statistically analyzed: the 91 elderly patients had significantly lower good prognosis rate 90 d after onset (20.9% vs. 36.3%) and MCE incidence (12.4% vs. 33.3%) than the 91 non-elderly patients ( P<0.05); there was no significant differences in successful vascular recanalization rate (67.0% vs. 71.4%), sICH incidence (15.7% vs. 17.6%) or mortality 90 d after onset (39.6% vs. 37.4%) between the two groups ( P>0.05). (2) Among the 680 patients, 314 (46.2%) had good prognosis and 366 (53.8%) had poor prognosis. As compared with the good prognosis group, the poor prognosis group had significantly higher proportion of patients at advanced age, significantly lower proportion of male patients, significantly higher proportion of patients with hypertension, diabetes or atrial fibrillation, significantly lower baseline Alberta Stroke early CT (ASPECT) scores, significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, statistically higher proportion of patients with cardiogenic embolism, significantly lower incidence of tandem lesions, significantly shorter time from onset to sheathing, statistically higher proportion of internal carotid artery occlusion, significantly lower proportion of patients with grading 2 collateral circulation, and significantly lower proportion of successful vascular recanalization ( P<0.05). Advanced age ( OR=3.144, 95%CI: 1.675-5.900, P<0.001) was an independent factor for prognoses 90 d after MT, in addition to baseline ASPECT scores, baseline NIHSS scores, diabetes mellitus, successful recanalization, and collateral circulation grading. (3) In the advanced age group, there were 19 patients (20.7%) with good prognosis and 73 patients (79.3%) with poor prognosis. As compared with the good prognosis subgroup, the poor prognosis subgroup had significantly lower proportion of male patients, significantly lower proportion of patients with grading 2 collateral circulation or complete recanalization, and significantly higher baseline NIHSS scores ( P<0.05). Baseline NIHSS score ( OR=1.482, 95%CI: 1.187-1.850, P=0.001) was an independent factor for prognoses 90 d after MT in advanced age patients. Conclusion:Although advanced age is an independent risk factor for prognoses of patients with acute anterior circulation ALVOS accepted MT, there are still some advanced age patients benefiting from MT without increased complications, especially for those with low baseline NIHSS scores.